GSK-3β Inhibitors Attenuate the PM2.5-Induced Inflammatory Response in Bronchial Epithelial Cells

Background and Purpose: PM2.5-associated airway inflammation has recently been recognized as pivotal to the development of COPD. Aberrant glycogen synthase kinase (GSK)-3 beta signaling is linked to the inflammatory response. Therefore, we investigated the effects of GSK-3 beta inhibitors on the PM2.5-induced inflammatory response in bronchial epithelial cells. Methods: The production of phosphorylated GSK-3 beta (p-GSK-3 beta) was analyzed by immunohistochemistry with PM2.5-induced mice. HBECs were treated with various inhibitors targeting GSK-3 beta or JNK before PM2.5 stimulation. The production of GSK-3 beta signaling was analyzed by Western blotting. Inflammatory cytokine production was detected by qRT-PCR and ELISA. Results: PM2.5 exposure caused lung inflammation, upregulated serum concentrations of HMGB1 and IL-6, decreased IL-10 expression, and significantly attenuated p-GSK-3 beta production in mice. HBECs exposed to PM2.5 showed significantly reduced p-GSK-3 beta production, an increased ratio of p-JNK/JNK, increased NF-kappa B activation and I.B degradation, and upregulated the inflammatory cytokines HMGB1 and IL-6. Intervention with GSK-3 beta inhibitors TDZD-8 and SB216763 significantly suppressed PM2.5-induced outcomes. Moreover, the JNK inhibitor SP600125 also reduced the level of NF-kappa B phosphorylation induced by PM2.5. The differences in the levels of inflammation-related cytokines in the TDZD-8 groups were greater than those in the SB216763 groups. Conclusion: Inhibition of GSK-3 beta weakens the PM2.5-induced inflammatory response by regulating the JNK/NF-.B signaling pathway in bronchial epithelial cells.

Automated summary

Inhibition of GSK-3 beta weakens the PM2.5-induced inflammatory response by regulating the JNK/NF-kappa B signaling pathway in bronchial epithelial cells. The use of GSK-3 beta inhibitors TDZD-8 and SB216763 significantly suppressed the effects of PM2.5 on inflammation, with TDZD-8 showing greater differences in inflammation-related cytokine levels compared to SB216763. JNK inhibitor SP600125 also reduced the level of NF-kappa B phosphorylation induced by PM2.5.